Metabolic tolerance

Detection times vary depending on analytical method used, drug metabolism, tolerance, patient s condition, fluid intake and method and frequency of ingestion. These are general guidelines only. 

Tolerance—decreased responsiveness to a drug following repeated exposure—is a common feature of sedative-hypnotic use. It may result in the need for an increase in the dose required to maintain symptomatic improvement or to promote sleep. It is important to recognize that partial cross-tolerance occurs between the sedative-hypnotics described here and also with ethanol (see Chapter 23)—a feature of some clinical importance, as explained below. The mechanisms responsible for tolerance to sedative-hypnotics are not well understood. An increase in the rate of drug metabolism (metabolic tolerance) may be partly responsible in the case of chronic administration of barbiturates, but changes in responsiveness of the central nervous system (pharmacodynamic tolerance) are of greater importance for most sedative-hypnotics. In the case of benzodiazepines, the development of tolerance in animals has been associated with down-regulation of brain benzodiazepine receptors. Tolerance has been reported to occur with the extended use of zolpidem. Minimal tolerance was observed with the use of zaleplon over a 5-week period and eszopiclone over a 6-month period. 

Our sample collection strategy using both SCUBA and CCUBA targets two types of locations unexplored depth zones and stressful environments. Water temperatures are known to affect faunal communities of a region significantly, primarily due to the narrow metabolic tolerance of most marine species. We take advantage of this diversity to gather samples from... 

Psychological tolerance is the term used to describe the reduction in the desired psychological effects of the drug this may not be paralleled by an increase in the metabolic tolerance. 

Psychological tolerance to alcohol develops at a faster rate than metabolic tolerance. Thus death from alcohol overdose can occur in a psychologically tolerant person following only a moderate increase in alcohol intake above that normally consumed. 

An acute dose of 100-200 mg morphine, or its equivalent, in the non-tolerant adult can lead to respiratory depression, coma and death. In the tolerant individual, single doses or more than 10 times this amount are tolerated and have little visible effect. The development of tolerance to the opiates does not appear to be due to enhanced metabolism (metabolic tolerance) but is probably due to opioid receptor insensitivity (tissue tolerance). The dependent person therefore ultimately requires high doses of the opiate to prevent withdrawal effects. 

Tetrahydrocannabinol is metabolized in the liver to form active metabolites which are further metabolized to inactive polar compounds these are excreted in the urine. Some metabolites are excreted into the bile and then recycled via the enterohepatic circulation. Because of their high lipophilicity, most active metabolites are widely distributed in fat deposits and the brain, from which sources they are only slowly eliminated. The half-life of elimination for many of the active metabolites has been calculated to be approximately 30 hours. Accordingly, accumulation occurs with regular, chronic dosing. Traces of the cannabinoids can be detected in the blood and urine of users for many days after the last administration. There is some evidence of metabolic tolerance occurring after chronic use of the drug. THC and related cannabinoids readily penetrate the placental barrier and may possibly detrimentally affect foetal development. 

Regular use of cannabis can lead to an intake of THC which would be toxic to the naive user. This suggests that tolerance develops. While there is some evidence that metabolic tolerance may arise, it would appear that tissue... 

Reduced effect of an agonist or antagonist following its prolonged administration resulting from the increased metabolism (called metabolic tolerance) or decreased receptor sensitivity (termed pharmaco- or tissue tolerance). 

The microsomal ethanol-oxidizing system (MEOS) becomes significant in terms of ethanol metabolism only at blood levels in excess of 100 mg/dL. Chronic exposure to ethanol increases the activity of MEOS, and this effect may be contributory to metabolic tolerance. None of the other enzymes involved in ethanol metabolism change their activities with chronic use. Ethanol induces the formation of certain cytochrome P450 isozymes if used regularly. The answer is (C). 

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